Mouse brain stem cells capable of converting into blood vessel cells

Adult stem cells in the brains of mice possess a broader differentiation potential than previously thought and may be capable of developing into other cell types including those involved in the formation of new blood vessels, according to a new study supported by the National Institute on Aging (NIA), a part of the National Institutes of Health. The finding could help resolve a critical question about these promising, but still mystifying cells.

The report by Fred H. Gage, Ph.D., and colleagues at the Salk Institute in La Jolla, CA, and Kumamoto University in Japan, appears in the July 15, 2004, issue of Nature.

Adult stem cells in the brain were proposed to be restricted to the generation of neurons and cells, such as glial cells, that support neuron function. Experiments over the past several years have raised the possibility that stem cells from the brain may be able to give rise to additional cell types, a phenomenon known as plasticity. But recent findings have challenged this theory, suggesting that many of these stem cells merely merge or “fuse” with an existing cell within a tissue forming a hybrid that takes on the pre-existing cell’s functions.

“Resolving this issue is important because fused cells may have a different therapeutic potential than stem cells that differentiate into new cells, says Bradley C. Wise, Ph.D., of the NIA’s Neuroscience and Neuropsychology of Aging Program. “While this new finding doesn’t fully answer this vital question, it keeps open the possibility that adult stem cells from different organs one day may be harnessed to help prevent and treat neurological disorders.”

In their experiments, Gage and his colleagues grew mouse brain stem cells, which form neurons and glial cells, in the same culture dishes with human endothelial cells, which form the lining of blood vessels. Over time, about 6 percent of the mouse neural stem cells began to show signs that they had developed into cells similar to endothelial cells. The new cells expressed CD146, Flk-1 and VE Cadherin, protein markers that are associated with endothelial cells. They also retained a single nucleus and had only mouse chromosomes, suggesting they had converted into a different type of cell rather than merged with an existing human endothelial cell. Similar results were seen when these same neural stem cells were transplanted into the brains of mice early in development.